Pentoxifylline in patients with ulcerative colitis treated with mesalamine by modulation of IL-6/STAT3, ZO-1, and S1P pathways: a randomized controlled double-blinded study.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that lasts a long time and has a variety of causes. AIM: The primary aim of this study was to evaluate pentoxifylline's (PTX) essential function in patients with UC. METHODS: Fifty-two mild to moderate UC patients who matched the eligibility requirements participated in this clinical study. One gram of mesalamine (t.i.d.) and a placebo were administered to the mesalamine group (n = 26) for a duration of 24 weeks. Mesalamine 1 g t.i.d. and PTX 400 mg two times daily were administered to the PTX group (n = 26) for 24 weeks. A gastroenterologist investigated patients at the start and 6 months after the medication was given to assess disease activity index (DAI) and numeric pain rating scale (NRS). Also, interleukin-6 (IL-6), sphingosine 1 phosphate (S1P), tumor necrosis factor-alpha (TNF-α), and fecal myeloperoxidase (MPO) were measured before and after therapy. Zonula occuldin-1 (ZO-1) and signal transducer and activator of transcription factor-3 (STAT-3) expression was assessed before and after therapy as well as histological assessment. Short Form 36 Health Survey (SF-36), was assessed for each patient before and after 6 months of treatment. RESULTS: The PTX group showed statistically lower levels of serum SIP, TNF-α, IL-6, faecal MPO, gene expression of STAT-3, and a significant increase of ZO-1 in comparison with the mesalamine group. DAI and NRS significantly decreased whereas SF-36 significantly increased in the PTX group. CONCLUSION: PTX could alleviate inflammation in patients with UC, so it might be promising adjunctive for patients with UC. TRIAL REGISTRATION IDENTIFIER: NCT05558761.

Repurposing metformin as adjuvant therapy in patients with ulcerative colitis treated with mesalamine: A randomized controlled double-blinded study.

BACKGROUND: Ulcerative colitis (UC) is a type of inflammatory bowel disease associated with persistent inflammation. Animal studies proved the efficacy of metformin in UC. AIM: To investigate the potential role of metformin and its protective pathways in patients with UC. METHODS: This is a randomized, controlled, and double-blinded clinical trial that included 60 participants with mild to moderate UC and was divided randomly into two groups (n = 30). For 6 months, the mesalamine group received 1 g of mesalamine three times daily (t.i.d.). For six months, the metformin group received mesalamine 1 g t.i.d. and metformin 500 mg twice daily. A gastroenterologist evaluated patients at baseline and 6 months after starting the treatment in order to measure serum levels of zonulin, sphingosine 1 phosphate (S1P), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Biopsies from the colon were used to measure gene expression of zonula occuldin-1 (ZO-1), signal transducer and activator of factor-3 (STAT-3), and intracellular adhesion molecule-1 (ICAM-1). The numeric pain rating scale (NRS) and partial Mayo score were also assessed for each patient. RESULTS: When compared to the mesalamine group, the metformin group demonstrated a statistical decrease in serum IL-6, zonulin, TNF-α, SIP, gene expression of ICAM-1 and STAT-3, and a significant increase in colonic ZO-1 when compared to the mesalamine group. The metformin group also showed a significant decrease in NRS and partial Mayo score index in comparison with the mesalamine group. CONCLUSION: Metformin may be a promising additional therapy for UC patients. Trial registration identifier: NCT05553704.

Inflammatory bowel disease evolution in the past two decades: a chronological multinational study.

Background: The multifactorial nature of inflammatory bowel disease (IBD), which manifests differently in individuals creates a need for a better understanding of the behaviour and pattern of the disease due to environmental factors. The current study aimed to study the changes in IBD behaviour, presentation, and characteristics in patients over the past two decades with a goal of improving patients' diagnosis, management and outcomes. Methods: During a 6-month period (1/02/2022-30/07/2022), the information of patients with IBD who attended IBD outpatient clinics of 11 referral centre's in six countries was collected, and based on the first time of diagnosis with IBD, they were allocated as group A (those who were diagnosed more than 15 years ago), group B (those who were diagnosed with IBD between 5 and 15 years ago) and group C (IBD cases who diagnosed in recent 5 years). Then the most prevalent subtypes and characters of the disease are evaluated and compared to make clear if the presenting pattern and behaviour of the disease has changed in the last 2 decades. Findings: Overall 1430 patients with IBD including 1207 patients with ulcerative colitis (UC) (84.5%) and 205 patients with Crohn's disease (CD; 14.3%) included. Mean age of participants at the first time of diagnosis with IBD was 30 years. The extra-intestinal involvement of IBD in groups A and B was more prevalent in comparison with group C. Most of those in groups A & B had academic education but in group C, the most prevalent educational status was high school or diploma (P = 0.012). In contrast to groups A and B, the relative prevalence of medium socioeconomic level in group C had decreased (65%). Relative prevalence of UC subtypes was similar among groups A and B (extensive colitis as most prevalent) but in group C, the most prevalent subtype is left side colitis (38.17%). The most prevalent subtype of CD in groups A and B was ileocolic involvement while in group C, upper GI involvement is significantly increased. The rate of food sensitivity among groups A and B was more than group C (P = 0.00001). The relative prevalence of patients with no flare has increased with a steady slope (P < 0.00001). Relative prevalence of presenting symptoms among patients with UC in group C differs and nowadays the rate abdominal pain (70.7%) and bloating (43.9%) have increased and frequency of diarrhoea (67.4%) has decreased. Interpretation: In the recent 5 years, the pattern of UC presentation has changed. The rate of upper GI involvement in CD and relative prevalence of patients with no disease flare increased and the rate of extra intestinal involvement decreased. Funding: None.

Clinico-Epidemiological Characteristics of Patients With Inflammatory Bowel Disease in Egypt: A Nationwide Multicenter Study.

Background and Aims: Ulcerative colitis (UC) and Crohn's disease (CD) are the most common types of Inflammatory bowel disease (IBD), with variable responses to traditional therapies and unpredicted prognosis. In Egypt and most developing countries, the lack of recent epidemiological and prognostic data adversely affects management strategies. We collected and analyzed data of patients with IBD from multiple centers across Egypt to evaluate patients' clinical and epidemiological characteristics. Methods: This retrospective multicenter study included patients diagnosed with IBD between May 2018 and August 2021, at 14 tertiary gastroenterology units across Egypt. Record analysis addressed a combination of clinico-epidemiological characteristics, biochemical tests, stool markers, endoscopic features, histological information, and different lines for IBD treatment. Results: We identified 1104 patients with an established diagnosis of IBD; 81% of them had UC, and 19% showed CD. The mean age of onset was 35.1 ± 12.5 years ranging from 5 to 88 years, the mean duration of illness at inclusion was 13.6 ± 16.7 years, gender distribution was almost equal with a significant male dominance (60.4%, p = 0.003) among patients with CD, 57% were living in rural areas, and 70.5% were from Delta and Coastal areas. Two hundred nineteen patients (19.8%) displayed comorbid conditions, primarily associated with CD. The most frequent complaints were diarrhea (73.2%), rectal bleeding (54.6%) that was significantly higher among patients with UC (64%, p < 0.001), and 46.8% with abdominal pain (more often with CD: 71%, p < 0.001). Conventional therapy was effective in treating 94.7% of patients. The main lesion in patients with CD was ileal (47.8%); patients with UC mainly exhibited proctosigmoiditis (28.4%). Dysplasia was detected in 7.2% of patients, mainly subjects with UC. Conclusions: To our knowledge, our effort is the first and largest cohort of Egyptian patients with IBD to describe clinical and epidemiological characteristics, and diagnostic and management approaches. More extensive prospective studies are still needed to fully characterize disease distribution, environmental factors, and pathological features of the disease.

Acute cytomegalovirus infection is a risk factor in refractory and complicated inflammatory bowel disease.

The role of cytomegalovirus (CMV) infection in patients with inflammatory bowel disease (IBD) is controversial. Although CMV has been specifically associated with refractory disease, the strength and nature of this association have been a subject of debate. The aim of this study was to evaluate the prevalence and outcome of acute cytomegalovirus infection in patients with severe refractory and complicated inflammatory bowel disease. Seventy-two patients with active IBD (both ulcerative colitis [UC] and Crohn's diseases [CD]) were included in this study. Thorough history taking and physical examination of all patients was made with special emphasis on symptoms and signs of CMV disease. Colonoscopic assessment was made for the extent and activity of IBD and collection of specimen. Prevalence of CMV infection was estimated by serology; anti-CMV IgM and IgG antibodies, and pathologic studies of colonic biopsies used conventional haematoxylin and eosin (H & E) and immunohistochemistry (IHC) with monoclonal antibodies. Complete blood count and liver function tests were done for all patients. Among 72 patients with active inflammatory bowel disease, 23 (31.9%) were resistant to intravenous steroids. CMV was detected in eight (six with UC and two with CD) of the 23 (34.8%) steroid-resistant patients and in only one (3.2%) patient in the remaining 31 patients under steroid treatment and was not detected in 18 IBD patients not using steroids. Among nine CMV-positive IBD patients, six (66.6%) were female and six had fever; cervical lymphadenopathy was found in five patients and splenomegaly in two, compared to no patients in the CMV-negative group (P = 0.01 and 0.03, respectively). Leucopenia and thrombocytopenia were predominantly seen in the CMV-positive versus CMV-negative patients (2.1+/-0.3 vs. 5.9+/-3.4 and 98+/-34 vs. 165+/-101, respectively). Pancolitis was found in five of nine CMV-positive IBD patients whereas in only two patients out of 63 in the CMV-negative group (P = 0.005). Acute CMV infection in patients with IBD is not rare and is often underestimated. CMV infection in patients with refractory or complicated IBD should be ruled out before aggressive immunosuppressive therapy. High clinical index of suspicion for the association of CMV infection with IBD should be directed towards female IBD patients presenting with fever, lymphadenopathy, splenomegaly, leucopenia, and mild hepatitis. CMV IHC is significantly more sensitive than routine H & E stain and should be considered as part of the routine evaluation of IBD patients with severe exacerbation or steroid-refractory disease before proceeding with other medical or surgical therapy that may not be necessary once the CMV is treated.

Inflammatory bowel disease: review and future view.

Inflammatory bowel disease (IBD) is chronic problem that cause an inflammation of the intestines. Significant progress has been made in recent years to the field of IBD epidemiology, pathogenesis and treatment and a number of new insights have been created. Also, there is an increasing interest in the discovery of different new aspects related diagnosis and treatment. In this review we will highlight few points related to current situation of inflammatory bowel disease and some areas of progress in different fields.

Oxidative stress and inflammatory bowel disease.

Inflammatory Bowel Disease (IBD) is a chronic relapsing and remitting inflammatory condition of the gastrointestinal tract. The exact cause of IBD remains undetermined, the condition appears to be related to a combination of genetic and environmental factors. While many gaps in our knowledge still exist, the last two decades have witnessed an unprecedented progress not only in the etiology ; but mainly in the mechanisms underlying the chronic inflammatory response, immunologic and genetic aspects. We review some recent points of research in pathogenesis with special stress on oxidative stress and its correlations with disease activity.

Study of respiratory disorders in endoscopically negative and positive gastroesophageal reflux disease.

BACKGROUND/AIM: The relation between respiratory disorders and reflux symptoms has been debated since the beginning of the last century and the interest in this question has increased during the last few decades. This study aims to investigate the relation between specified respiratory disorders and reflux symptoms and examine the correlations between respiratory disorders and endoscopic findings in patients with gastroesophageal reflux disease. PATIENTS AND METHODS: This study included 515 patients evaluated for gastroesophageal reflux disease (GERD) by patient self-report symptom questionnaire; modified four grade Likert scale and endoscopic assessment using endoscopic Los Angeles Classification. All participants were asked about various respiratory symptoms experienced during the past six months and exposed to measuring body mass index (BMI), medical history, pulmonary physical examination, chest X-ray, respiratory function tests and available sleep studies. RESULTS: A total number of 515 patients were categorized according to endoscopic findings into two groups; (group1) subjects with normal endoscopic studies (NERD) 118 (22.9%) patients and (group2) subjects with abnormal endoscopic studies (ERD) 397 (77.1%). The proportion of females was significantly higher in ERD group (80.1%) as compared with NERD group (62.7%) ( P < 0.02). Duration of reflux symptoms found to be significantly prolonged in ERD group ( P < 0.03). The cases of ERD group were more likely to be overweight (BMI>25) P < 0.02. History of pulmonary symptoms preceding GERD symptoms was found in 15% of patients. There were 294 patients (57.1%) with different pulmonary manifestations. These manifestations were significantly higher among female group ( P < 0.01) and among obese, above 40 years old ( P < 0.001, 0.05 respectively). Among all patients with respiratory manifestations the commonest disorders diagnosed were chronic pharyngitis (50.3%), chronic bronchitis (15.8%), bronchial asthma (12.6%) and recurrent pneumonia (3.3%). Obstructive sleep apnea and recurrent hemoptysis were present in 2.7% and 1.5% of the studied patients respectively. There were three cases of chronic lung abscess. There was a significant difference between ERD and NERD groups in their relations to respiratory disorders ( P < 0.001). There were statistically significant differences in FEV1, FVC and FEV1/FVC ( P < 0.02, P < 0.05 and P < 0.05) respectively in ERD group as compared with NERD group. CONCLUSION: The study confirms the strong link between gastroesophageal reflux symptoms and various respiratory disorders. Endoscopy of the upper digestive tract remains an important exam in the evaluation of GERD. Respiratory symptoms are more prevalent among erosive esophagitis patients with a positive correlation with degree of severity. There is direct relationship between the severity of airways obstruction as detected by FEV1 and FEV1/FVC and GER symptoms.

Simplified Early Predictors of Severe Acute Pancreatitis: A Prospective Study.

BACKGROUND: To propose simple tests for the prediction of severe acute pancreatitis (SAP), which are accurate and could be performed at emergency departments and outpatient clinics. METHODS: A prospective study was performed on 149 patients admitted with acute pancreatitis. Body mass index (BMI), plain chest radiograph, blood biochemical data were obtained at the time of admission; white cell, lymphocyte and platelet counts, hematocrit level, prothrombin time, PaO2, creatinine, calcium, blood sugar, total protein, aspartate aminotransferase, total bilirubin, amylase, lipase and C-reaction protein were determined. Patients were graded into severe and mild acute pancreatitis based on CT Balthazar grading system. RESULTS: Twenty-seven patients were diagnosed to have SAP and 122 patients considered mild acute pancreatitis. Comparing parameters between both groups; significant factors (P < 0.05) were blood sugar level, haematocrit level, BMI and presence of pleural effusion in chest X-ray. The hematocrit at admission and at approximately 24 hours was significantly higher among patients with SAP. Twenty-two of 27 cases of severe disease and only 10 of 122 cases of mild acute pancreatitis diagnosed to have pleural effusion (P < 0.001). CONCLUSION: BMI, blood glucose ≥ 190 mg/dL, hematocrit level ≥ 43 % and pleural effusion detected by plain chest radiograph are simple tests and provide significant predictive power for clinical decision-making.

Study of Chronic Hepatopathy in Patients With Sickle Cell Disease.

BACKGROUND: Hepatic lesions in sickle cell disease were studied essentially in autopsy specimens. We investigated chronic hepatopathy in living adults with sickle cell disease and report the clinical, biochemical, and hepatic histological findings in these patients. METHODS: A total of 170 adult patients with sickle cell syndrome were prospectively investigated. Clinical and laboratory investigation including liver function tests, serological tests for viral hepatitis, autoimmune hepatitis, and abdominal ultrasonography were performed in all of the patients. Liver biopsies were studied from 27 patients. RESULTS: There was clinical evidence of jaundice in 123 (72.4%) patients, 118 (69.4%) patients had palpable liver, and 69% percent of the patients had elevated enzymes. Serological tests demonstrated the presence of hepatitis B infection in 18 (10.6%) patients and hepatitis C infection in 39 (23%) patients, serological markers for autoimmune hepatitis were positive in two female patients, one diagnosed chronic intrahepatic cholestasis. All 27 biopsies presented some degree of sickling hepatopathy. Moderate or marked liver siderosis was associated with the number of transfusions. CONCLUSIONS: The clinical spectrum of sickle cell disease ranges from mild liver function test abnormalities to significant hepatic abnormalities with marked hyperbilirubinemia. Multiple factors may contribute to the etiology of the liver disease, including ischemia, transfusion related viral hepatitis, iron overload, and gallstones.

Assessment of thrombophilic abnormalities during the active state of inflammatory bowel disease.

BACKGROUND/AIMS: Thromboembolic disease has been recognized as a complication of inflammatory bowel disease (IBD). The relative contributions of inherited or acquired thrombophilia and the inflammatory response to the mechanism of this tendency are unclear. Thrombotic events are more common in active disease although significant numbers also occur spontaneously. The aim of this study was to investigate common thrombophilic markers in patients with active IBD. METHODS: Twenty-six patients with IBD who had active disease, and 40 sex- and age-matched non-IBD patients were recruited into the study. For all the subjects, complete blood counts, C-reactive protein levels, erythrocyte sedimentation rate, International normalized ratio, activated partial thromboplastin time, and levels of lupus anticoagulant, anticardiolipin antibodies (ACA IgG), proteins C and S, antithrombin-III (AT-III), and factor V were measured. RESULTS: The International normalized ratio, activated partial thromboplastin time, and levels of proteins C and S were comparable between the two groups. However, antithrombin-III levels were significantly lower in the IBD group as compared with that in the healthy control group (P < 0.001). ACA IgG was detected in one patient in the IBD group. Factor V Leiden mutation was present in 3.8% of the patients in the IBD group, whereas the prevalence was 2.5% in the control group. Significantly elevated platelet counts were observed in patients with active Crohn's disease compared with that in the control group (P < 0.001), but they were not significantly increased in active ulcerative colitis (P = 0.231). CONCLUSIONS: The present study failed to establish a strong association between the common thrombophilic markers and the active clinical course of IBD, with the exception of high platelet counts and lower levels of AT-III in the IBD group as compared with those in the control group. All other parameters of thrombophilia were comparable between the two groups.

Black esophagus: a case report.

The black esophagus is a rare observation during upper endoscopy. We describe a case of a male with chronic obstructive pulmonary disease, hypertension, diabetes, acute renal failure and in septic state, who developed a black esophagus after hypotensive episodes. The clinical, endoscopic and histopathological characteristics are presented.